Balance between Id and E proteins regulates myeloid-versus-lymphoid lineage decisions.
Hematopoiesis consists of a series of lineage decisions controlled by specific gene expression that is regulated by transcription factors and intracellular signaling events in response to environmental cues. Here, we demonstrate that the balance between E-protein transcription factors and their inhibitors, Id proteins, is important for the myeloid-versus-lymphoid fate choice. Using Id1-GFP knockin mice, we show that transcription of the Id1 gene begins to be up-regulated at the granulocyte-macrophage progenitor stage and continues throughout myelopoiesis. Id1 expression is also stimulated by cytokines favoring myeloid differentiation. Forced expression of Id1 in multipotent progenitors promotes myeloid development and suppresses B-cell formation. Conversely, enhancing E-protein activity by expressing a variant of E47 resistant to Id-mediated inhibition prevents the myeloid cell fate while driving B-cell differentiation from lymphoid-primed multipotent progenitors. Together, these results suggest a crucial function for E proteins in the myeloid-versus-lymphoid lineage decision.
Cochrane
Shawn W
SW
Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Zhao
Ying
Y
Welner
Robert S
RS
Sun
Xiao-Hong
XH
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D038042:Myelopoiesis / Q000502:physiology*; D051820:TCF Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D058125:Transcription Factor 7-Like 1 Protein
C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein